tbuckley/cabot-search huggingface dataset:
Immunogenicity of the vaccine against Sars-Cov-2 in cancer patients under active treatment.
Authors: María Leonor Fernandez-Murga, Lucia Serrano-Garcia, Javier Garde-Noguera, Maria Portero, José García-Sánchez, Lorena Regal, Victoria Dominguez-Martinez, Antonio Llombart-Cussac
Journal: Journal of Clinical Oncology (2022)

e13632 Background: Coranavirus disease 2019 (COVID-19) has affected more than 220 millon people worldwide. The establishment of safe and effective vaccine coverage is crucial in these patients. We aim to investigate the safety, adverse effects and immune response (cellular and humoral) in cancer patients under active treatment and risk criteria. Methods: 56 samples from cancer patients under active treatment for cancer were collected before and after vaccination Demographic, clinical and biochemical data were collected and a post-vaccination symptomatology questionnaire was performed. For the determination of anti-SARS-Cov-2 antibodies (Immunoglobulin G and immunoglobulin M) we used the ELISA technique (LIASON SARS-CoV-2 S1/S2 IgG test and LIASON SARS-CoV-2 IgM test, DiaSorin, Saluggia, Italy). A study of the lymphocyte population was performed by flow cytometry. Results: We enrolled 52 patients with cancer who received mRNA vaccines (mRNA-1273 and BNT162b2), 2 patients with AZD1222vaccine and 2 with Ad26.COV2.S vaccine. All patients were SARS-COV-2 naive as determined by a negative anti-SARS-COVID-2 IgG test baseline. The median follow-up time was 50 days after receip of a second vaccine dosis. All subject received anti- cancer therapy. The most common anti-cancer treatment received by this cohort of patients was cytotoxic chemoterapy (44.6%), immunotherapy (25%), and monoclonal antibody therapy (14.3%). Overall, a high rate of seroconvertion(anti–IgG) (94,5%) was observed in our cohort, 1 patients with chemotherapy (1,8%) and 2 patients with immunotherapy (3,6%) were negatives. No significant differences in antibody titer were observed according to therapy. Thirty percent presented an antibody titer lower than 1000 U/ml, 27 (48%) patients developed an anti-SARS-CoV2 titer between 1000-4000 U/ml, and only 9 (16%) subjects presented a titer higher than 4000 U/ml. Studies of the lymphocyte profile of vaccinated patients showed no significant changes in the subtypes, except for peripheral memory CD3+ CD8+ lymphocytes which were significantly increased (p = 0.0001) after the second dose of anti-SARS-CoV-2 vaccine. Interestingly, cell apoptosis was significantly reduced in almost all T lymphocyte subtypes studied in vaccinated patients. Finally, analysis of blood cells showed a statistically significant increase (p = 0.0402) of eosinophils in vaccinated patients compared to baseline data. Conclusions: A personalized approach to vaccination can be proposed to cancer patients, especially depending on the type of tumor and the specific oncological treatments received. We are currently recruiting patients (n = 150) who have received the third dose of vaccine and plan to follow up at 6 months for humoral and cellular immune response. Final results will be reported at the ASCO meeting.
Insights of clinical significance from solid tumor profiles with FoundationOneCDx.
Authors: Andreas M Heilmann, Jonathan W. Riess, Molly McLaughlin-Drubin, James Creeden, Brian Michael Alexander, Rachel Erlich
Journal: Journal of Clinical Oncology (2022)

3126 Background: FoundationOne CDx (F1CDx) is a US FDA-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. Tumor profiling with F1CDx detects genomic findings with evidence of additional clinical significance. This study analyzes the breadth and impact of clinical decision insights from F1CDx clinical reports across solid tumors. Methods: F1CDx consecutive reports (n = 109,695) were retrospectively analyzed for the type and frequency of clinically significant predictive, prognostic, and diagnostic genomic alterations and signatures in common cancer types and across solid tumors. Predictive markers were defined as therapeutically relevant markers in drug labels or NCCN guidelines or targets of ESCAT evidence Tier I/II (Mateo et al., 2018; PMID: 30137196). Prognostic and diagnostic markers were determined in accordance with NCCN, ESMO, or WHO guidelines. We also describe the frequency and targets of interventional clinical trials with targeted therapies or immune checkpoint inhibitors that were matched to tumor profiles based on clinical or strong preclinical evidence. Results: Predictive genomic findings of clinical significance were identified in more than half of non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), and melanoma (MEL) tissue samples; over a third of ovarian cancer (OC), urothelial carcinoma (UC), and head and neck squamous cell carcinoma (HNSCC); approximately a fourth of prostate cancer (PC), gastro-esophageal adenocarcinoma (GEA), cholangiocarcinoma (CA), and glioma (GL) samples; and one in 18 pancreatic adenocarcinoma (PA) samples (Table). Prognostic markers were reported for patients with NSCLC (18%), CRC (10%), BC (16%), PC (25%), CA (8.1%), MEL (24%), GL (74%), or HNSCC (7.1%). Diagnostic markers were frequently detected for patients with GL and noted for patients with BC, GEA, or MEL (Table). Interventional clinical trials were evidence-matched to most F1CDx tumor profiles (89%, range 82% in PC to 99% in PA), with the targets of approved therapies accounting for a small subset of targets in clinical development. Conclusions: F1CDx reports support clinical decision making by interpreting predictive, prognostic, and diagnostic markers according to professional guidelines as well as investigational markers for the enrollment in clinical trials. [Table: see text]
Attacking effect of diabetes mellitus and chronic neurogenic pain on malignant process:Are mitochondria of the heart damaged?
Authors: Irina V. Neskubina, Elena M. Frantsiyants, Irina V. Kaplieva, Natalia D. Cheryarina, Ekaterina I. Surikova, Alla I. Shikhlyarova, Valeria A. Bandovkina, Yulia A. Pogorelova, Ludmila A. Nemashkalova, Lidia K. Trepitaki, Polina S. Kachesova, Inga Movlievna Kotieva, Maria I. Morozova, Yuriy V. Przhedetskiy, Galina V. Zhukova, Irina A. Goroshinskaya, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e21557 Background: Mitochondrial dysfunction is one of the mechanisms for the development of heart disease that requires close study. Diabetic cardiomyopathy is the leading cause of death in such patients due to the development of heart failure. Chronic pain may be associated with higher prevalence of cardiovascular disease, and little is known about its potential biological consequences. The purpose of this study was to analyze parameters of free radical oxidation and mitochondrial respiration in heart cells in experimental animals with malignant tumors growing in presence of diabetes mellitus (DM) and chronic neurogenic pain. Methods: The study included outbred female rats (n = 32) weighing 180-220 g and C57BL/6 female mice (n = 84) weighing 21-22 g. Experimental groups of rats were: intact animals (n = 8), controls (n = 8) with DM, comparison group (n = 8) with subcutaneously inoculated Guerin’s carcinoma, and main group (n = 8) with Guerin’s carcinoma subcutaneously inoculated after 1 week of persistent hypothyroidism. Experimental groups of mice were: intact animals (n = 21), controls (n = 21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation, comparison group (n = 21) with subcutaneously inoculated melanoma (B16/F10), and main group (n = 21) with melanoma subcutaneously inoculated 3 weeks after the CNP model was created (CNP+B16/F10). Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/g of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/g of protein), and malondialdehyde (MDA) (nM/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program. Results: DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (p &lt; 0.05) and downregulated cytochrome C by 1.5 times (p &lt; 0.05) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (p &lt; 0.05) and decreased cytochrome C by 1.5 times (p &lt; 0.05), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (p &lt; 0.05) and decreased cytochrome C by 1.6 times (p &lt; 0.05) in heart cell mitochondria. Conclusions: Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells which results in DNA damage and destabilization of the respiratory chain mediated by free radical oxidation processes.
Biomarker testing patterns among patients with early and late-onset metastatic colon cancer.
Authors: Hina Mohammed, Connor Sweetnam, Jeanna Wallenta Law, Liz Toland, Anna B. Berry, Thomas D. Brown, Chenan Zhang
Journal: Journal of Clinical Oncology (2022)

e15575 Background: Molecular testing is essential in considering targeted therapies, particularly for the increasing number of metastatic colon cancer (mCC) patients (pts) diagnosed at younger ages who may present with more aggressive disease. This analysis compares demographic and clinical characteristics, and biomarker testing and positivity rates of mCC pts diagnosed at younger versus older ages. Methods: We analyzed 1029 pts with mCC (stage IV at diagnosis) between 01/01/2016 - 12/31/2020 who received care in community health systems in the United States. Pts 18-49 years at mCC diagnosis were considered early onset (EO), and those 50 or older were considered late onset (LO). We compared the distributions of year at diagnosis, gender, race/ethnicity, smoking status, histology, stage at diagnosis, tumor sidedness, KRAS, NRAS, and BRAF testing, and positivity rates between EO and LO mCC pts. Differences in distributions were assessed using chi-square tests. Results: EO pts (n = 148) were more likely to have left-sided tumors than LO pts (n = 881, 55% vs. 36%; p-value &lt; 0.001), and were less likely to be ever smokers (24% vs. 40%; p-value &lt; 0.001); the remaining demographic and clinical characteristics were similar between the two groups. Testing was significantly more common among EO than LO pts for KRAS (71% vs 48%), NRAS (39% vs 29%), and BRAF (41% vs 31%) (Table). Annual NRAS and BRAF testing rates increased between 2016 - 2020 for both groups: NRAS rates increased from 13% to 41%, and 5% to 37%, for EO and LO pts, respectively; BRAF rates increased from 13% to 41%, and 5% to 40%, for EO and LO pts, respectively. KRAS testing rates held at a consistent rate over time for EO pts, and increased over time among LO mCC pts (35% - 52%). The positivity rates for KRAS, NRAS and BRAF mutations were similar among tested pts in both groups. Conclusions: In this real world analysis, pts with EO mCC were more likely to have left sided primary cancers, and less likely to have a smoking history. Of note, BRAF testing showed a marked increase over time among all mCC pts. EO pts were more likely to receive KRAS, NRAS and BRAF testing. Further understanding of the correlates of EO mCC, biomarker testing practices, and subsequent treatment decisions is critical to improving pt outcomes.[Table: see text]
Antitumor activity of sunvozertinib in NSCLC patients with EGFR Exon20 insertion mutations after platinum and anti-PD(L)1 treatment failures.
Authors: Pasi A. Janne, Mengzhao Wang, D. Ross Camidge, Paul Mitchell, Jian Fang, Weiqi Nian, Chao-Hua Chiu, Jianying Zhou, Yanqiu Zhao, Wu-Chou Su, Tsung-Ying Yang, Viola Weijia Zhu, Michael Millward, Yun Fan, Wen-Tsung Huang, Ying Cheng, Liyan Jiang, Daniel Brungs, Li Zheng, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2022)

9015 Background: Platinum-based chemotherapy is the 1 st line standard of care for NSCLC patients with EGFR exon 20 insertion mutations (Exon20ins), with anti-PD(L)1 frequently used as well. Here we present anti-tumor activity of sunvozertinib in these patients whose disease had progressed on these therapies from two ongoing phase 1/2 studies (WK-KONG1, NCT03974022 and WU-KONG2, CTR20192097). Based on these data, sunvozertinib was granted the Breakthrough Therapy Designation by both US FDA and China NMPA. Methods: The objective of this study is to characterize the safety and efficacy of sunvozertinib in platinum-pretreated advanced NSCLC patients harboring EGFR Exon20ins, with or without anti-PD(L1) treatment. In addition, the effect of prior treatment on sunvozertinib’s safety and efficacy were explored. Results: As of July 30, 2021, a total of 52 locally advanced or metastatic NSCLC patients harboring EGFR Exon20ins post platinum treatment were enrolled into WU-KONG1 and WU-KONG2 studies, and included in the efficacy analysis set (dose range: 50 mg to 400 mg, once daily). Male/Female: 21/31; Median age 59; Asian/White: 44/8; Prior therapies: median 2.5 (range 1-10); 31% received prior anti-PD(L)1 treatment (all in £ 300 mg cohorts); 40% of the subjects with baseline brain metastasis. Partial response was observed at ≥ 100 mg. At the dose level of 100 mg, 200 mg, 300 mg and 400 mg, confirmed ORR was 50% (1/2), 55.6 % (5/9), 44.8% (13/29) and 22.2% (2/9), respectively. With a median follow-up time of 10.5 months, median DoR was not reached for 200 mg cohort; with a median follow-up of 7 months, median DoR of 300 mg group was 5.6 months. Progression free survival (PFS) rate at 6 months for 100 mg, 200 mg, 300 mg and 400 mg cohorts was 50%, 53.3%, 44.6% and 44.4%, respectively. In patients with/without prior anti-PD(L)1 treatment, comparable efficacy and safety profiles were observed. Conclusions: The data suggest sunvozertinib is active in platinum-pretreated patients with EGFR Exon20ins, irrespective of prior or after anti-PD(L)1 treatment. The updated data will be presented at the meeting. Sunvozertinib is currently in phase 2 pivotal clinical development (NCT03974022 and China CTR20211009). Clinical trial information: NCT03974022.
INSP-04. Confirmatory adaptive designs for survival trials with several time-to-event endpoints
Authors: Rene Schmidt
Journal: Neuro-Oncology (2022)

Abstract Confirmatory adaptive designs comprise a range of statistical methods that allow to modify the sample size of an ongoing trial in a data-dependent way without compromising control of the type I error rate. For short-term endpoints (e.g., 3-month response rate), comprehensive methodology of adaptive designs exists. However, clinical trials in oncology often have a special focus on long-term outcome and therefore often choose a time-to-event endpoint as the primary endpoint. Typical examples are progression-free survival (PFS) or overall survival (OS). But subtle statistical problems arise when adaptively analysing survival trials. Classical designs for survival trials are therefore commonly limited to a single primary endpoint, which combines the occurrence of progression, toxicities, deaths, and other events of potential interest into a single statistical measure (composite endpoint). However, the complexity of oncological diseases can be mapped more accurately using multi-stage models, where the occurrence of progressions, toxicities and deaths is modelled jointly instead of combining them into a single composite endpoint. We present and discuss adaptive design methodology for single-arm phase II survival trials for testing hypotheses on the joint distribution of several time-to-event endpoints in the context of multi-state models. We illustrate the methodology using the example of adaptive hypothesis tests for the joint distribution of progression-free survival (PFS) and overall survival (OS) in the context of an illness-death model. The methodology is motivated from application in pediatric oncology.
Medications mostly associated with Urinary Tract Infections (UTIs): assessment of the EudraVigilance (EV) and Food and Drug Administration (FDA) Pharmacovigilance databases entries
Authors: C. De Nunzio, A. Cicione, F. Di Giacomo, R. Lombardo, G. Disabato, O.A. Voglino, S. D'Annunzio, V. Baldassarri, A. Franco, L. Rovesti, E. Mancini, G. Guarnotta, A. Guercio, G. Gallo, J. Stira, B. Turchi, C. Gravina, A. Tubaro
Journal: European Urology (2022)
Real-life omalizumab exposure and discontinuation in a large nationwide population-based study of paediatric and adult asthma patients
Authors: Marc Humbert, Arnaud Bourdin, Camille Taillé, Driss Kamar, Céline Thonnelier, Audrey Lajoinie, Alexandre Rigault, Antoine Deschildre, Mathieu Molimard
Journal: European Respiratory Journal (2022)

Background This real-life study aimed to assess omalizumab treatment patterns in adult and paediatric asthma patients, and to describe asthma control and healthcare resource use (HCRU) at omalizumab initiation and discontinuation. Methods The French healthcare database system (Système National des Données de Santé (SNDS)) was used to identify asthma patients aged ≥6 years who initiated omalizumab for at least 16 weeks from 2009 to 2019. We examined omalizumab treatment patterns using dispensation records. Results We identified 16 750 adults and 2453 children initiating omalizumab. Median treatment persistence before discontinuation (T STOP ) was 51.2 (95% CI 49.3–53.4) months in adults and 53.7 (95% CI 50.6–56.4) months in children. At 2 years of omalizumab exposure, rate of hospitalisation for asthma decreased by 75% and use of oral corticosteroids (OCS) by 30%, in adults and children. Among adults who discontinued omalizumab while asthma was controlled, 70%, 39% and 24% remained controlled and did not resume omalizumab at 1, 2 and 3 years after discontinuation, respectively. These proportions were higher in children (76%, 44% and 33%, respectively). Over 2 years of follow-up after discontinuation, HCRU remained stable in adults and children, notably rate of hospitalisations for asthma (none before T STOP , 1.3% and 0.6% at 2 years) and use of OCS (in adults and children, respectively: 20.0% and 20.2% before T STOP , 33.3% and 24.6% at 2 years). Conclusion This is the first large-scale study describing omalizumab real-life exposure patterns in adult and paediatric asthma patients in France with &gt;10 years of follow-up. We showed the long-term maintenance of low HCRU in adults and children who discontinued omalizumab while asthma was controlled, notably for OCS use and hospitalisations for asthma.
Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma
Authors: Jiangchao Wu, Xun Wang, Li Chen, Jianing Wang, Junlei Zhang, Jianghui Tang, Yongtao Ji, Jinyuan Song, Lin Wang, Yaxing Zhao, Hui Zhang, Taohong Li, Jianpeng Sheng, Dong Chen, Qi Zhang, Tingbo Liang
Journal: Bioactive Materials (2022)

Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade (ICB).Here, we synthesized polydopamine-nanoparticle-stabilized oxygen microcapsules with excellent stabilization, bioavailability, and biocompatibility for direct oxygen delivery into tumor sites by interfacial polymerization.We observed oxygen microcapsules enhanced the oxygen concentration in the hypoxia environment and maintained the oxygen concentration for a long period both in vitro and in vivo. We found that oxygen microcapsules could significantly improve the efficiency of ICB against PDAC in vivo. Mechanismly, combined treatments using oxygen microcapsules and ICB could reduce the infiltration of tumor-associated macrophages (TAMs) and polarized pro-tumor M2 macrophages into anti-tumor M1 macrophages. In addition, combined treatments could elevate the proportion of T helper subtype 1 cells (Th1 cells) and cytotoxic T lymphocytes cells (CTLs) to mediate anti-tumor immune response in TME.In summary, this pre-clinical study indicated that reversing hypoxia in TME by using oxygen microcapsules was an effective strategy to improve the performances of ICB on PDAC, which holds great potential for treating PDAC in the future.
Robot-assisted partial nephrectomy for multiple renal tumors – a multicenter analysis
Authors: N.N. Harke, F. Schiefelbein, A. Schneller, G. Schoen, C.G. Wiesinger, J. Pfuner, E. Falkensammer, N. Gilbert, A. Eraky, V. Zimmermanns, I. Paramythelli, B.A. Hadaschik, J.P. Radtke, C. Darr, M.C. Kriegmair, M. Flintrop, M. Wolters, P. Faraj Tabrizi, M.A. Kuczyk, D. Osmonov
Journal: European Urology (2022)
Oncologic emergencies and urgencies: A comprehensive review
Authors: Bonnie E. Gould Rothberg, Tammie E. Quest, Sai‐Ching J. Yeung, Lorraine C. Pelosof, David E. Gerber, Justin A. Seltzer, Jason J. Bischof, Charles R. Thomas, Nausheen Akhter, Mira Mamtani, Robin E. Stutman, Christopher W. Baugh, Venkataraman Anantharaman, Nicholas R. Pettit, Adam D. Klotz, Michael A. Gibbs, Demetrios N. Kyriacou
Journal: CA A Cancer Journal for Clinicians (2022)

Abstract Patients with advanced cancer generate 4 million visits annually to emergency departments (EDs) and other dedicated, high‐acuity oncology urgent care centers. Because of both the increasing complexity of systemic treatments overall and the higher rates of active therapy in the geriatric population, many patients experiencing acute decompensations are frail and acutely ill. This article comprehensively reviews the spectrum of oncologic emergencies and urgencies typically encountered in acute care settings. Presentation, underlying etiology, and up‐to‐date clinical pathways are discussed. Criteria for either a safe discharge to home or a transition of care to the inpatient oncology hospitalist team are emphasized. This review extends beyond familiar conditions such as febrile neutropenia, hypercalcemia, tumor lysis syndrome, malignant spinal cord compression, mechanical bowel obstruction, and breakthrough pain crises to include a broader spectrum of topics encompassing the syndrome of inappropriate antidiuretic hormone secretion, venous thromboembolism and malignant effusions, as well as chemotherapy‐induced mucositis, cardiomyopathy, nausea, vomiting, and diarrhea. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug‐conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T‐cells, are summarized. Finally, strategies for facilitating same‐day direct admission to hospice from the ED are discussed. This article not only can serve as a point‐of‐care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit.